Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 virus strains has geographical diversity associated with diverse severity, mortality rate, and response to treatment that were characterized using phylogenetic network analysis of SARS-CoV-2 genomes. Although, there is no explicit and integrative explanation for these variations, the genetic arrangement, and stability of SARS-CoV-2 are basic contributing factors to its virulence and pathogenesis. Hence, understanding these features can be used to predict the future transmission dynamics of SARS-CoV-2 infection, drug development, and vaccine. In this review, we discuss the most recent findings on the mutations in the SARS-CoV-2, which provide valuable information on the genetic diversity of SARS-CoV-2, especially for DNA-based diagnosis, antivirals, and vaccine development for COVID-19.